Improving the Understanding of Platinum Sensitivity and the Tumour Microenvironment in High Grade Serous Ovarian Cancer PDF Download

Author: Malcolm John Farquharson
Publisher:
ISBN:
Category : Ovaries
Languages : en
Pages : 273

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Author: M. Sharon Stack
Publisher: MDPI
ISBN: 3038975540
Category : Biology (General)
Languages : en
Pages : 435

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Book Description
This book is a printed edition of the Special Issue "The Tumor Microenvironment of High Grade Serous Ovarian Cancer" that was published in Cancers

Author: Goli Samimi
Publisher: Academic Press
ISBN: 0128198419
Category : Science
Languages : en
Pages : 190

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Book Description
Overcoming Ovarian Cancer Chemoresistance presents non-overlapping review chapters that discuss the state of the field in overcoming chemoresistance of ovarian cancer and treatment options before and following recurrence, considering the genetic makeup of the ovarian cancer patient and her tumor. With the uptake of both germline and somatic gene testing, clinicians can obtain a more comprehensive understanding of ovarian tumors and this book provides information to link the genetic makeup of a tumor (or patient) with the best available treatment. The book discusses topics such as strategies to fight chemo-resistance in ovarian cancer, circulating DNA as a monitor of response, BRCA mutations, ovarian cancer stem cells, immunotherapy and vaccines. Additionally, it brings a list of promising agents at clinical and pre-clinical stage that will impact the treatment in the near future. This book is a valuable source for cancer researchers, oncologists and several members of biomedical field who need to understand how to battle chemoresistance in ovarian cancer. Provides a comprehensive view of both biological and genetic determinants of resistance, as well as technical approaches to monitor response Discusses genetic reversions as a unique alteration and a new field of study Includes a chapter on upcoming and promising agents that are in the pre-clinical and early clinical space, to set the stage for future directions in the field

Author: Viive Maarika Howell
Publisher: Frontiers Media SA
ISBN: 2889197697
Category : Medicine (General)
Languages : en
Pages : 178

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Book Description
This eBook provides a compendium of the current state-of-the-art in research tools for, and understanding of, the critical research areas in epithelial ovarian cancer (EOC) with a strong emphasis on (HG-SOC). Research areas covered include therapy response and development, microenvironmental influences and the etiology and progression of EOC. Ten articles detail established and novel in vivo and in vitro model systems. These include primary and immortalized cell culture in 2D and 3D as well as genetically engineered, transgenic, spontaneous, syngeneic, classical xenograft and patient derived xenograft mouse models. The generation of genetically engineered mouse models of HG-SOC has been a major dilemma as models with the oncogenic aberrations common in the human malignancy do not accurately recapitulate HG-SOC. Conversely, commonly used HG-SOC cell lines have been found to not harbor the expected genetic changes. These issues as well as the rapid acceptance of patient derived xenograft models are reviewed. Five articles discuss different aspects of the tumor microenvironment including its role in therapy resistance, disease progression and metastasis. Mutation of BRCA1/2 continues to be the best defined risk factor for HG-SOC. Three articles discuss BRCA-loss in the context of disease development, targeted therapies and changes in preventative measures proposed for mutation carriers in light of the recent advances in knowledge regarding the origins of this malignancy. An image of HG-SOC with reduced BRCA1 expression is featured on the cover (image by VM Howell). A major clinical issue for patients with HG-SOC is the development of therapy resistance. Five articles focus on therapy resistance and different ways to overcome resistance. Overall, this eBook is an outstanding resource to aid researchers design their programs of research and determine the most appropriate and up-to-date EOC model systems to address their research questions.

Author: Kenneth P. Nephew
Publisher:
ISBN: 9783038975557
Category : Electronic books
Languages : en
Pages : 1

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Book Description
The Special Issue on high grade serous ovarian cancer (HGSOC) and the contribution of the tumor microenviroment (TME) consists of reviews contributed by leaders in the OC field. As HGSOC metastases have a highly complex TME, there is an urgent need to better understand the TME in general, its distinct components in particular, and the role of the TME in the context of disease recurrence and development of chemoresistance. The Special Issue incorporates the current understanding of the different parts of thd TME components, including the cancer cells themselves, the cells surrounding the cancer cells or stromal cells, and the cells of the immune system, which are attracted to the site of metastases. In addition to these cells of the TME, the role of various cellular factors made by the cells of the TME are also the subject of the reviews. In addition, reviews in this Special Issue cover the complex relationships between the molecular mechanisms of HGSOC progression, including genomic, epigenomic and transcriptomic changes and changes in the immune cell landscape, as these may provide attractive new molecular targets for HGSOC therapy.

Author: National Academies of Sciences, Engineering, and Medicine
Publisher: National Academies Press
ISBN: 0309380499
Category : Medical
Languages : en
Pages : 397

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Book Description
In an era of promising advances in cancer research, there are considerable and even alarming gaps in the fundamental knowledge and understanding of ovarian cancer. Researchers now know that ovarian cancer is not a single disease-several distinct subtypes exist with different origins, risk factors, genetic mutations, biological behaviors, and prognoses. However, persistent questions have impeded progress toward improving the prevention, early detection, treatment, and management of ovarian cancers. Failure to significantly improve morbidity and mortality during the past several decades is likely due to several factors, including the lack of research being performed by specific disease subtype, lack of definitive knowledge of the cell of origin and disease progression, and incomplete understanding of genetic and non-genetic risk factors. Ovarian Cancers examines the state of the science in ovarian cancer research, identifies key gaps in the evidence base and the challenges to addressing those gaps, considers opportunities for advancing ovarian cancer research, and examines avenues for translation and dissemination of new findings and communication of new information to patients and others. This study makes recommendations for public- and private-sector efforts that could facilitate progress in reducing the incidence of morbidity and mortality from ovarian cancers.

Author: Khalid El Bairi
Publisher: Springer Nature
ISBN: 9811618739
Category : Medical
Languages : en
Pages : 236

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Book Description
This book comprehensively summarizes the biology, etiology, and pathology of ovarian cancer and explores the role of deep molecular and cellular profiling in the advancement of precision medicine. The initial chapter discusses our current understanding of the origin, development, progression and tumorigenesis of ovarian cancer. In turn, the book highlights the development of resistance, disease occurrence, and poor prognosis that are the hallmarks of ovarian cancer. The book then reviews the role of deep molecular and cellular profiling to overcome challenges that are associated with the treatment of ovarian cancer. It explores the use of genome-wide association analysis to identify genetic variants for the evaluation of ovarian carcinoma risk and prognostic prediction. Lastly, it highlights various diagnostic and prognostic ovarian cancer biomarkers for the development of molecular-targeted therapy.

Author: Julian Smazynski
Publisher:
ISBN:
Category :
Languages : en
Pages :

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Book Description
High-grade serous ovarian cancer (HGSC) remains the most common and lethal subtype of ovarian cancer with a 5-year survival rate of ~30%, highlighting an urgent need for new treatments. Cancer immunotherapy has emerged as an efficacious strategy aimed at harnessing the exquisite capabilities of our immune system to destroy malignant cells. However, the development of more effective immunotherapies is hampered by our limited understanding of the phenotype of bona fide tumor-reactive T cells versus irrelevant bystanders. Further, T cells that exhibit tumor specificity appear to encompass a tissue resident memory (TRM) phenotype but combat a harsh immunosuppressive tumor microenvironment, often leading to an exhausted phenotypic state and evasion of immune-mediated destruction. These insights have led to rapid clinical implementation of so-called "checkpoint blockade" therapies that re-invigorate T cell-mediated tumor destruction by blocking surface inhibitory receptors or ligands. Thus, by identifying the phenotype of prognostically favourable TRM T cells and the immunosuppressive networks they face, my thesis work tackles a critical challenge in designing the next generation of therapeutic interventions for this disease. To address this challenge, I hypothesized that (1) the TRM phenotype could be modulated for improving adoptive T cell therapy; (2) TRM TIL characterized by the co-expression of CD103, PD-1, and CD39 in HGSC provide improved prognostic benefit indicative of enriched tumor reactivity; (3) the TIGIT/CD155 signalling axis plays a crucial role in shaping the immunosuppressive landscape impeding TRM T cells in HGSC. Firstly, I developed methods for modulating the TRM phenotype on expanded human and murine T cells for adoptive cell therapy and assessed the therapeutic impact of these phenotypes. Secondly, we applied high-dimensional flow cytometry, single-cell sequencing, and multiplexed immunofluorescence to primary human HGSC specimens to explore the single-cell phenotypic profiles and prognostic significance of tumor-infiltrating T cells co-expressing three putative markers of tumor reactivity: CD39, CD103, and PD-1. These 'triple-positive' T cells exhibited a highly activated/exhausted phenotype and superior prognostic value relative to all other T-cell subsets, suggesting these markers enrich for tumor-reactive clones. Furthermore, these triple-positive cells exhibited heightened expression of the inhibitory checkpoint TIGIT, which plays a prominent role in tumor-mediated immune suppression. Finally, to explore the therapeutic implications of this finding, we investigated the relationship between the TIGIT signaling axis on TIL and prognosis in HGSC. Once again utilizing high-dimensional flow cytometry, multi-color histological imaging, and gene expression profiling we found T cells from HGSC frequently express TIGIT ex vivo and post-clinical expansion. Further, CD155, the dominant ligand for TIGIT, was largely expressed on malignant epithelium in HGSC and showed a negative association with immune infiltration. Thus, TRM T cells represents a compelling immunotherapeutic immune subset in HGSC and one that could be bolstered by immune checkpoint inhibition of the TIGIT/CD155 axis.

Author: Hidetaka Katabuchi
Publisher: Springer
ISBN: 9811041601
Category : Medical
Languages : en
Pages : 313

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Book Description
This volume presents the latest advances and the current status of our understanding regarding ovarian cancer, addressing both the basic and clinical aspects of the disease. In terms of basic medicine, the WHO Classification of Tumors of Female Reproductive Organs was revised in 2014, and that version addresses several new concepts and histopathological classifications not previously included. One of the most revolutionary breakthroughs concerns the genesis of epithelial ovarian tumors, shifting the focus from the ovarian surface epithelium to serous tubal intraepithelial carcinomas. Clinically, the mortality rate of epithelial ovarian cancer has gradually increased over the past few decades, making it essential to pursue multidisciplinary treatment and apply novel techniques such as neoadjuvant chemotherapy in daily clinical practice. The primary clinical task is the effective treatment of recurrent ovarian cancer with early palliative medicine. Fertility-sparing surgery may also be pursued depending on histologic subtypes, stage, extent of disease, and preexisting ovarian reserve with the concept of oncofertility. On the basis of the considerations described above, each expert author elucidates the science of ovarian cancer in detail, thus providing a collection that will benefit young medical oncologists and seasoned gynecologists and obstetricians alike.

Author: Omer Devaja
Publisher: BoD – Books on Demand
ISBN: 1789843332
Category : Medical
Languages : en
Pages : 366

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Book Description
Ovarian cancer management is a rapidly changing field with new treatment agents available as a result of a greater understanding of the pathogenesis of this disease. In addition, both surgical and chemotherapeutic treatment strategies are evolving to maximise response in this disease. This book brings together leading specialists from around the world to discuss and outline a variety of new concepts in ovarian cancer, ranging from molecular biology and genetics through screening to both surgical and chemotherapeutic management.